At the neuromuscular junction, the transmission of signal from the nerve to the muscle which causes muscle contraction is mediated by the release of acetylcholine from the nerve terminal and the sensing of this molecule by the receptors in the muscle. To gain insight into the formation of the neuromuscular junction, this study will use physiological and structural techniques to observe the development of the acetylcholine receptors in muscle cells in tissue culture and the interaction between the nerve and the muscle during innervation. We are particularly interested in the information that the nerve cell conveys to the muscle in causing an accumulation of acetylcholine receptors in the postjunctional membrane and the mechanism that the muscle cell uses in generating such a receptor accumulation. Besides conventional nerve-muscle cocultures, we will also study the formation of the acetylcholine receptor clusters induced by polypeptide-coated latex beads and by constant electric field. Previous studies have shown that these agents also cause a local post-junctional membrane-type differentiation. These studies are aimed at providing a fundamental understanding of the development of the muscle during the formation of neuromuscular junction. This knowledge is essential for the elucidation of the cause of many neuromuscular disorders.